1,2-diO-n-hexyl-3-O-benzyl-sn-glycerol | 124186-29-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 英文名称: 1,2-diO-n-hexyl-3-O-benzyl-sn-glycerol
• 英文别名: (R)-1-benzyloxy-2,3-bis(hexyloxy)propane；(2R)-3-O-benzyl-1,2-di-O-hexyl-sn-glycerol；[(2R)-2,3-dihexoxypropoxy]methylbenzene
• CAS: 124186-29-4
• 化学式: C₂₂H₃₈O₃
• 分子量: 350.542
• InChiKey: ZINVZXWTLPJHFF-JOCHJYFZSA-N

物化性质

• 沸点：
  436.1±35.0 °C(Predicted)
• 密度：
  0.940±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  25
• 可旋转键数：
  17
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2-diO-n-hexyl-3-O-benzyl-sn-glycerol 在 palladium on activated charcoal 四氮唑 、 4-二甲氨基吡啶 、 氢气 、 三乙胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， -40.0~20.0 ℃ 、344.74 kPa 条件下， 反应 28.0h， 生成 4-N-3'-O-di(tert-butoxycarbonyl)-5'-O-succinyl-[2-O-1,3-bis-(1,2-di-O-hexyl-sn-glycero-3-phosphoryl)glycerol dimethyl ether] gemcitabine
  参考文献：
  名称：

  Synthesis and biological evaluation of gemcitabine–lipid conjugate (NEO6002)

  摘要：

  A novel gemcitabine-lipid conjugate 5 was synthesized and tested for its in vivo efficacy and toxicity. Compound 5 was tested in BxPC-3 human pancreatic tumor model in SCID mice and exhibited promising activity and lower toxicity when compared with Gerrizar (R). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.03.046
• 作为产物：
  描述：

  溴己烷 、 (R)-(+)-3-苄氧基-1,2-丙二醇 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以70%的产率得到1,2-diO-n-hexyl-3-O-benzyl-sn-glycerol
  参考文献：
  名称：

  Design and synthesis of lipid-coupled inositol 1,2,3,4,5,6-hexakisphosphate derivatives exhibiting high-affinity binding for the HIV-1 MA domain

  摘要：

  脂质偶联的肌醇1,2,3,4,5,6-六磷酸酯通过静电作用和疏水作用紧密结合到HIV-1 MA。

  DOI：

  10.1039/c4ob00350k

文献信息

• Nonhydrolyzable analogs of phosphatidylinositol as ligands of phospholipases C
  作者：Cornelia Mihai、Xiangjun Yue、Li Zhao、Alex Kravchuk、Ming-Daw Tsai、Karol S. Bruzik

  DOI：10.1039/b9nj00629j

  日期：——

  Phosphatidylinositol-specific phospholipases C (PI-PLCs) are important enzymes participating in transmembrane signal transduction. The structures of the two major species of these enzymes: bacterial Ca2+-nondependent enzyme from B. cereus and mammalian Ca2+-dependent PLCδ1 from rat brain in the complexes with the polar head groups of their substrates have been previously solved. Although these structures show few differences as compared to free enzymes, there is a compelling evidence that full catalytic activity of PI-PLC necessitates interaction of the enzyme with the entire substrate, including the hydrophobic fatty acid chains. In this work we develop new tightly binding and cleavage-resistant analogs of phosphatidylinositol, using relatively minor modifications of the structure. Two synthesized analogs, 2-amino-2-deoxy-PI (8) and the conformationally constrained analog (10) had binding affinities (Ki) in 10 μM range. 15N-1H HSQC NMR spectra of uniformly 15N-labeled bacterial Ca2+-nondependent and Ca2+-dependent phospholipases C, btPLC and saPLC1, respectively, displayed changes upon ligand binding that suggest an occurrence of a conformational change.

  磷脂酰肌醇特异性磷脂酶 C（PI-PLCs）是参与跨膜信号转导的重要酶。这些酶的两个主要种类：来自 B. cereus 的不依赖 Ca2+ 的细菌酶和来自大鼠大脑的依赖 Ca2+ 的哺乳动物 PLCδ1 与其底物极性头基的复合物的结构以前已经解决。虽然这些结构与游离酶相比几乎没有什么不同，但有令人信服的证据表明，PI-PLC 的全部催化活性需要酶与整个底物（包括疏水性脂肪酸链）的相互作用。在这项工作中，我们对磷脂酰肌醇的结构进行了相对较小的修改，开发出了新的紧密结合且抗裂解的类似物。合成的两种类似物--2-氨基-2-脱氧-PI（8）和构象约束类似物（10）的结合亲和力（Ki）在 10 μM 范围内。15N-1H HSQC NMR 光谱显示，15N 标记的细菌 Ca2+ 非依赖性磷脂酶 C 和 Ca2+ 依赖性磷脂酶 C（btPLC 和 saPLC1）在与配体结合后发生了变化，表明发生了构象变化。
• [EN] NUCLEOSIDE-LIPID CONJUGATES, THEIR METHOD OF PREPARATION AND USES THEREOF<br/>[FR] CONJUGUES NUCLEOSIDE-LIPIDE, LEUR PROCEDE DE PREPARATION, ET LEURS UTILISATIONS
  申请人：NEOPHARM INC

  公开号：WO2006029081A3

  公开（公告）日：2009-04-23
• Inhibition of human erythrocyte membrane phosphatidylinositol 4-kinase by phospholipid analogues
  作者：RC Young、CP Downes、M Jones、KJ Milliner、KK Rana、JG Ward

  DOI：10.1016/0223-5234(94)90146-5

  日期：1994.1

  Analogues of phosphatidylinositol (Ptdlns, 1) have been synthesized to investigate the structural requirements for inhibition of a Ptdlns 4-kinase obtained from human erythrocyte membranes. While the presence of either D-1 or D-3 Stereochemistry in the inositol moiety greatly influences the degree of inhibition produced by Ptdlns analogues, the stereochemistry of the glycerol moiety is of little consequence. Neither structural feature, however, makes a significant contribution to binding affinity. Competitive inhibitory activity was found to be retained (or even enhanced) in substantially simpler analogues consisting of 1 or 2 hydrocarbon chains attached to a charged phosphate head group, such as in the phosphatidic acids, 24 and 26. The observation that the phosphatidylinositol 4-phosphate (Ptdlns 4P) and phosphatidic acid analogues (eg, 16 or 17, and 26 respectively) inhibit Ptdlns 4-kinase may suggest that such species have a regulatory role in Ptdlns turnover.
• MIYADZAVA, TAKEHSI;ITO, MASAESI;SITORI, DZEHMIO;TOESIMA, AKI;ODZAVA, TOSI+
  作者：MIYADZAVA, TAKEHSI、ITO, MASAESI、SITORI, DZEHMIO、TOESIMA, AKI、ODZAVA, TOSI+

  DOI：——

  日期：——